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Brevetoxin inhalation alters the pulmonary response to influenza A in the male F344 rat.

Abstract
Epidemiological studies demonstrated that the number of emergency-room visits for respiratory indications increases during periods of Florida Red Tides. The purpose of this study was to examine whether or not repeated brevetoxin inhalation, as may occur during a Florida Red Tide, affects pulmonary responses to influenza A. Male F344 rats were divided into four groups: (1) sham aerosol/no influenza; (2) sham aerosol/influenza; (3) brevetoxin/no influenza; and (4) brevetoxin/influenza. Animals were exposed by nose-only inhalation to vehicle or 50 μg brevetoxin-3/m3, 2 h/d for 12 d. On d 6 of aerosol exposure, groups 2 and 4 were administered 10,000 plaque-forming units of influenza A, strain HKX-31 (H3N2), by intratracheal instillation. Subgroups were euthanized at 2, 4, and 7 d post influenza treatment. Lungs were evaluated for viral load, cytokine content, and histopathologic changes. Influenza virus was cleared from the lungs over the 7-d period; however, there was significantly more virus remaining in the group 4 lungs compared to group 2. Influenza virus significantly increased interleukins-1α and -6 and monocyte chemotactic protein-1 in lung; brevetoxin exposure significantly enhanced the influenza-induced response. At 7 d, the severity of perivascular and peribronchiolar inflammatory cell infiltrates was greatest in group 4. Bronchiolitis persisted, with low incidence and severity, only in group 4 at d 7. These results suggest that repeated inhalation exposure to brevetoxin may delay virus particle clearance and recovery from influenza A infection in the rat lung.
AuthorsJanet M Benson, Molly L Wolf, Adriana Kajon, Brad M Tibbetts, Andrea J Bourdelais, Daniel G Baden, Thomas H March
JournalJournal of toxicology and environmental health. Part A (J Toxicol Environ Health A) Vol. 74 Issue 5 Pg. 313-24 ( 2011) ISSN: 1528-7394 [Print] England
PMID21240731 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Cytokines
  • Marine Toxins
  • Oxocins
  • brevetoxin 3
Topics
  • Administration, Intranasal
  • Animals
  • Bronchiolitis, Viral (immunology, pathology, virology)
  • Cytokines (metabolism)
  • Disease Susceptibility
  • Harmful Algal Bloom
  • Immunity, Mucosal (drug effects)
  • Influenza A Virus, H3N2 Subtype (growth & development, immunology, isolation & purification)
  • Lung (drug effects, immunology, pathology, virology)
  • Male
  • Marine Toxins (administration & dosage, toxicity)
  • Orthomyxoviridae Infections (immunology, metabolism, pathology, virology)
  • Oxocins (administration & dosage, toxicity)
  • Random Allocation
  • Rats
  • Rats, Inbred F344
  • Time Factors
  • Viral Load

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